This project investigates the developmental neurobehavioral effects of analgesics used for pain relief during labor and delivery. A rhesus monkey model has been developed for induction and monitoring of labor, intrapartum administration of analgesics and neurobehavioral evaluations during the first year of life. During the last project year, a study was completed using epidural bupivacaine, the second most common form of obstetric analgesia in this country. Results from the neurobehavioral test battery indicated that bupivacaine did not affect neonatal status or cognitive functions in infancy. Bupivacaine did alter the course of neurobehavioral maturation at two important time periods during brain development. The increase in manipulatory activity that normally occurs at 2 months of age was delayed by bupivacaine. The increase in motor disturbance behaviors that normally occurs at 10 months of age was prolonged and exacerbated by bupivacaine. We also completed experiments in guinea pigs demonstrating that epidural bupivacaine administered to the dam reaches fetal brain and that accumulation in fetal brain depends on the maturity of the fetus. Finally, assays of plasma protein throughout pregnancy in rhesus demonstrated that alpha acid glycoprotein, the main serum binding protein of bupivacaine at low doses, more than doubles during late pregnancy, while albumin, the secondary serum binding protein, decreases by a similar percentage. Together these studies demonstrate that bupivacaine administered epidurally to the mother during labor reaches fetal brain and can have long term effects on behavioral maturation.